Thesis advisor: Amir H. Hoveyda / Chapter 1. In Situ Methylene Capping: A Key Strategy in Catalytic Stereoretentive Olefin MetathesisA general approach for in situ methylene capping that significantly expands the scope of catalyst-controlled stereoselective olefin metathesis is presented. By incorporation of stereodefined 2-butene as the capping reagent, the catechothiolate Ru complex is enabled to catalyze olefin metathesis reactions of terminal alkenes. Substrates bearing a carboxylic acid, an aldehyde, an aryl substituent, an α substituent were thus converted to the desired products in 47–88% yield and 90:10–98:2 Z:E selectivity. The capping strategy was also applied in ring-closing metathesis reactions leading to 14- to 21-membered macrocyclic alkenes (96:4–98:2 Z:E). The utility of this method was highlighted through synthesis of a platelet aggregate inhibitor and two members of the prostaglandin family compounds by cross-metathesis reaction, as well as a strained 14-membered ring stapled peptide by macrocyclic ring-closing metathesis. Examples of the corresponding E-selective cross-processes are provided as well. Chapter 2. Synthesis of Z- or E-Trisubstituted Allylic Alcohols and Ethers by Kinetically Controlled Catalytic Cross-MetathesisKinetically controlled Ru-catalyzed cross-metathesis reactions that generate Z- or E-trisubstituted alkenes are discussed. Reactions were catalyzed by catechothiolate Ru complex to generate trisubstituted allylic alcohols and ethers in up to 81% yield and >98% stereoisomeric purity. The approach is applicable to synthesis of products containing an alcohol, an aldehyde, a carboxylic acid or an alkenyl substituent. Mechanistic models that account for the observed trends in efficiency and stereoselectivity will be provided. Chapter 3. A New Ru-Based Catechothiolate Complex Bearing an Unsaturated NHC Ligand for Synthesis of Z-α,β-Unsaturated Carbonyl Compounds by Cross Metathesis Design and development of a new Ru catechothiolate complex that may be used to promote Z-selective cross-metathesis transformations that afford Z-α,β-unsaturated esters, acids, and amides (including Weinweb amides) are discussed. Comparison between Ru catechothiolate complexes with an unsaturated NHC and a saturated NHC ligand will be provided. Utility of the approach is demonstrated by an eight-step synthesis (15% overall yield) of an intermediate for synthesis of stagonolide E, and a five-step synthesis of a precursor to dihydrocompactin / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.